REM Sleep Deprivation the Complex

REM Sleep Deprivation

The complex neurochemistry of the sleep wake cycle has been researched much over the last few decades. It is clear that REM deprivation causes the brain cellular machinery to trigger various neurobiological responses involving selective expression of genes, down regulation and upregulation of neurotransmitters, as well as reorganization of excitatory synapses.

Sleep is an indispensable physiological function for all living beings. The rejuvenating and refreshing effects of sleep are well-known and over the last few decades there have been numerous research on sleep. The negative effects of sleep deprivation or sleep restriction have been analyzed by many researchers and we now understand some of the basic neurological mechanisms of sleep. It is well-known that sleep deprivation affects the thalamocortical circuits that are important for cognitive functions among other regions of the brain. Research has also documented decline in psychomotor performance due to sleep deprivation. If prolonged for long time, sleep deprivation is even fatal. Besides the well-known effects of sleep on the processing of memory, it also affects other biological processes such as immune function, energy metabolism, appetite and the expression of various genes. The neurotransmitters that are involved in the sleep wake cycle and the effects of sleep deprivation on these transmitters are the subjects of intense study in the field of neurobiology of sleep. A brief overview of some research studies pertaining to sleep deprivation and the neurotransmitter changes will provide better insight into the topic.

Sleep Deprivation (Literature Review)

The deprivation of REM (rapid eye movement sleep) causes several changes in the neurotransmitters of the brain. Neuronal changes are important in the transition between wakeful state to sleep state and vice versa. Majumdar et.al (2005) focused on the morphological effects of REM sleep deprivation on the neurons. This study observed that loss of REM affected different regions of the brain differently. It was found that regions of brain such as the locus coeruleus that are directly involved in the control of REM sleep are affected. It was also found that treatment with alpha1-adrenergic antagonist, prazosin helped reverse these changes. [Majumdar et.al (2005)] an earlier research by the same authors focused on the upregulation or down regulation of neurotransmitters such as norephinephirine, GABA and acetylcholine. For this purpose the researchers performed immunohistochemical estimations of tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD) and choline acetyl transferase (ChAT) the respective neurotransmitter enzymes in the locus coeruleus, pedunculopontine tegmentum and laterodorsal tegmentum and the medial preoptic regions of rat brain. The researchers observed a significant rise in the levels of TH and GAD only in the locus coeruleus area of the sleep-deprived rats when compared with the control group. [Majumdar et.al, (2003)]

Basheer et.al (1998) also studied the effects of REM deprivation on the neurochemical changes in the locus coeruleus region of the brain. The rats involved in the experiment were deprived of REM sleep for 1, 3 and 5 days and then killed and the levels of tyrosine hydroxylase (TH) and norepinephrine transporter (NET) mRNA were measured using in situ hybridization technique. There were considerable differences between the levels of TH and NET mRNA in the LC of the experimental and control group rats. Since the use of tricyclic antidepressants induces similar changes in levels of TH and NET mRNA, REM sleep deprivation could be useful as a therapy for depression. This research also shows that an increase in norepinephrine activity reduces REM sleep. [Basheer et.al (1998)]

2004 study by Pedrazzoli et.al focused on the effect of REM sleep deprivation on the levels of hippocampal beta-adrenergic receptors. It is already known from previous research that REM deprivation results in a significant reduction of beta-adrenergic receptors in the cortical region. For the study the researchers conducted binding of [3H]-dihydroalprenolol ([3H]-DHA to both the hippocampus as well as the brainstem membranes. Brain homogenates were prepared from rats that were sleep deprived for more than 96 hours. Non-specific binding of both the hippocampus and the brainstem homogenates was determined using DL-propranolol and L-isoproterenol respectively. A marked reduction in beta-adrenergic receptors in both the hippocampus and the brainstem regions were observed. Since similar down regulation of beta-adrenergic receptors is observed after anti-depressant therapy, results from this research further assert the usefulness of REM deprivation for depression therapy. [Pedrazzoli et.al, 2004]

While the above study discussed changes in levels of beta-adrenergic receptors, a research by Hip lide et.al studied the effects of REM deprivation on the binding changes among ?1-, ?2-, ?1- and ?2 adrenergic receptors in different regions of the brain. All the 91 rats used in the study were sleep deprived for 96 hours prior to the experiment. It was observed that the binding of [3H] prazosin to the ?1 receptors was not considerably different along the different regions of the brain but a mild reduction was observed. Similarly there was no significant difference in the binding to ?2 sites labeled as [3H] UK-14, 314 in all of the 91 observed areas but it showed a mild increase. However, the ?1- and ?2 receptors showed considerable reduction in binding. Data gathered using quantitative receptor autoradiography revealed that atleast in 13 of 69 brain regions, ?1 receptor binding was considerably reduced while similar reductions for ?2 receptor binding was observed in 25 of the 72 regions. This experiment confirms that norepinephrine receptors are affected by REM deprivation. [Hip lide et.al, 1998]